Post-translational modification and quality control in the rer (a)Polypeptide PDI Irreversibly misfolded Incorrect disulfide bonds Disulfide bonds are formed and rearranged PDI in the er lumen Only in er lumen is there a redox environment for oxidation of-Sh groups PDI: protein disulfide isomerase, found in Correct disulfide abundance in the er lumen
Quality control of of newly synthesized proteins--The role of N- linked glycosylation in ER protein folding OMPLETELY UNFOLDED FOLDI NORMALLY FOLDED ubiquitin EXIT ROM glucose UDP accessory exit glucosyl GLUCOSE transferase TRIMMING TOSO N-glycanase oligosaccharide ER LUMEN ER protein translog calmex ER LUMEN n misfolded protein ER membrane CYTOSOL
The unfolded-protein response 6 nuclear 1 MISFOLDED PROTEINS IN ER SIGNAL NUCLEUS envelope THE NEED FOR MORE ER CHAPERONES chaperone mRNA BY ACTIVATING A TRANSMEMBRANE KINASE 2 ACTIVATED KINASE TURNS INTO CYTOSOL AN ENDORIBONUCLEASE gene regulatory protein ER chaperone 3 ENDORIBONUCLEASE CUTS SPECIFIC RNA MOLECULES AT TWO POSITIONS mRNA REMOVING AN INTRON exon exon 4 TWO EXONS ARE LIGATED TO pre-mRNA FORM AN ACTIVE mRNA transmembrane 5 mRNA IS TRANSLATED TO MAKE A protein kinase 3 Intron GENE REGULATORY PROTEIN sensor ribonuclease PyYYP domain 6 GENE REGULATORY PROTEIN ENTERS NUCLEUS AND ACTIVATES GENES misfolded ENCODING ER CHAPERONES protein RR 2 ER LUMEN 7 CHAPERONES ARE MADE IN ER WHERE THEY HELP FOLD PROTEINS
Synthesis of membrane lipids > Most membrane lipids are synthesized enterely within the er ER GC M There are two exceptions (1) sphingomyelin and glycolipids (begins in ER; completed in Golgi); 2) some of the unique lipids of the Mit and ChI membranes(themself) >The membranes of different Organelles have markdly different Ipds composition Transport by budding:ER→GC、Ly、 PM Transport by phospholipid exchange proteins(PEP): ER-other organelles (including mit and Chl)
vSynthesis 0f membrane lipids ØMost membrane lipids are synthesized enterely within the ER. Ø There are two exceptions: (1) sphingomyelin and glycolipids, (begins in ER; completed in Golgi); (2) some of the unique lipids of the Mit and Chl membranes (themself). ØThe membranes of different 0rganelles have markdly different lipids composition. §Transport by budding：ER→GC、Ly、 PM §Transport by phospholipid exchange proteins(PEP)：ER→other organelles （including Mit and Chl）
The role of phospholipid translocators in lipid bilayer synthesis lA)ER MEMBRANE (B) PLASMA MEMBRANE CYTOSOL CELL EXTERIOR lipid bilayer of asymmetric lipid endoplasmic bilayer of plasma ticulum ER LUMEN CYTOSOL PHOSPHOLIPID SYNTHESIS DELIVERY OF ADDS TO CYTOSOLIC HALF NEW MEMBRANE OF THE BILAYER BY EXOCYTOSIS phospholipid translocators 000000000 Scramblase SCRAMBLASE CATALYZES FLIPPASE CATALYSES FLIPPING OF PHOSPHOLIPID FLIPPING OF SPECIFIC (ABC MOLECULES PHOSPHOLIPIDS TO CYTOPLASMIC MONOLAYER transporter Family) symmetric growth of both halves of bilay 000000
The role of phospholipid translocators in lipid bilayer synthesis phospholipid translocators = Scramblase (ABC transporter Family)